title: A distinct translation initiation mechanism generates cryptic peptides for immune surveillance.
abstract: MHC class I molecules present a comprehensive mixture of peptides on the cell surface for immune surveillance. The peptides represent the intracellular protein milieu produced by translation of endogenous mRNAs. Unexpectedly, the peptides are encoded not only in conventional AUG initiated translational reading frames but also in alternative cryptic reading frames. Here, we analyzed how ribosomes recognize and use cryptic initiation codons in the mRNA. We find that translation initiation complexes assemble at non-AUG codons but differ from canonical AUG initiation in response to specific inhibitors acting within the peptidyl transferase and decoding centers of the ribosome. Thus, cryptic translation at non-AUG start codons can utilize a distinct initiation mechanism which could be differentially regulated to provide peptides for immune surveillance.
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America.
authors.forename: Shelley R
authors.initials: SR
authors.lastname: Starck
authors.forename: Yongkai
authors.initials: Y
authors.lastname: Ow
authors.forename: Vivian
authors.initials: V
authors.lastname: Jiang
authors.forename: Maria
authors.initials: M
authors.lastname: Tokuyama
authors.forename: Mark
authors.initials: M
authors.lastname: Rivera
authors.forename: Xin
authors.initials: X
authors.lastname: Qi
authors.forename: Richard W
authors.initials: RW
authors.lastname: Roberts
authors.forename: Nilabh
authors.initials: N
authors.lastname: Shastri
mesh_terms: D000818:Animals; D018387:Codon, Initiator; D015395:Histocompatibility Antigens Class I; D006801:Humans; D007157:Immunologic Surveillance / Q000235:genetics*; D010442:Peptide Chain Initiation, Translational; D010455:Peptides / Q000276:immunology*; D010458:Peptidyl Transferases / Q000037:antagonists & inhibitors; D014176:Protein Biosynthesis / Q000276:immunology*; D012333:RNA, Messenger; D012270:Ribosomes / Q000235:genetics
chemical_list: D018387:Codon, Initiator; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D012333:RNA, Messenger; D010458:Peptidyl Transferases